背景:川崎病(KD)是5岁以下儿童的病因不明的血管炎。冠状动脉瘤(CAA)是KD的主要并发症。它不再是一种自限性疾病,因为它的心血管后遗症可能会持续到成年期。NLRP3是NLRP3炎症小体的关键蛋白,其参与无菌炎性疾病。本研究调查不同分期KD患者血清NLRP3水平,探讨NLRP3与临床指标的关系。
方法:本研究共纳入247名儿童。KD急性期123例,93名健康儿童组成健康对照(HC)组。在急性KD患者中,52患有冠状动脉动脉瘤(KD-CAA),71没有(KD-NCAA)。在IVIG和阿司匹林治疗后收集36例患者样品。此外,29例患者处于心血管后遗症期。酶联免疫吸附测定用于测量所有受试者的血清NLRP3水平。
结果:KD组血清NLRP3升高,KD-CAA亚组甚至高于KD-NCAA亚组急性期患者。当患者接受IVIG和阿司匹林治疗时,血清NLRP3下降,但是在恢复期(冠状动脉后遗症)阶段,血清NLRP3再次升高。冠状动脉直径≥6mm组的血清NLRP3高于直径<6mm组。血清NLRP3的ROC曲线表明了其在KD和KD-CAA预测中的实用性。
结论:NLRP3可能参与KD患儿KD和CAA的发生发展。瞄准NLRP3可能会缓解CAA,从而降低成年期心血管事件的风险。
BACKGROUND: Kawasaki disease (KD) is a vasculitis of unknown etiology in children aged under 5 years. Coronary arterial aneurysm (CAA) is the major complication of KD. It is no longer though to be a self-limiting disease because its cardiovascular sequelae might persist into adulthood. NLRP3 is a key protein of the NLRP3 inflammasome that participates in sterile inflammatory disease. This study investigated the serum levels of NLRP3 in patients with KD at different stages to explore the relationships between serum NLRP3 and clinical parameters.
METHODS: A total of 247 children enrolled in this study. There were 123 patients in the acute stage of KD, and 93 healthy children made up the healthy control (HC) group. Among the acute KD patients, 52 had coronary arterial aneurysm (KD-CAA) and 71 did not (KD-NCAA). 36 patient samples were collected after IVIG and aspirin treatment. Additionally, 29 patients were in the cardiovascular sequelae stage. Enzyme-linked immunosorbent assay was used to measure serum NLRP3 levels in all subjects.
RESULTS: Serum NLRP3 was elevated in the KD group and was even higher in the KD-CAA subgroup than in the KD-NCAA subgroup of acute-stage patients. Serum NLRP3 declined when the patients were treated with IVIG and aspirin, but during the convalescent (coronary sequelae) stage, serum NLRP3 re-increased. Serum NLRP3 was higher in the ≥ 6-mm-coronary-arterial-diameter group than that the < 6-mm-diameter group. The ROC curve of serum NLRP3 indicated its utility in the prediction of both KD and KD-CAA.
CONCLUSIONS: NLRP3 may be involved in the development of KD and CAA in children with KD. Targeting NLRP3 might mitigate CAA, thereby reducing the risk of cardiovascular events in adulthood.